Premenopausal women with breast cancer in the early post-partum period show molecular profiles of invasion and are associated with poor prognosis

PURPOSE: Young premenopausal women develop breast cancer (BC) within 5–10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients are largely unknown. METHODS: We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (n = 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways. RESULTS: Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (p = 0.015 and p = 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors. CONCLUSION: Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-023-06956-6.